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Reg IV

Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 23 December 2011, last major update December 2011
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.


● Member of Regenerating protein family, which was originally isolated from regenerating rat pancreatic islets (J Biol Chem 1988;263:2111)
● Group of small, multifunctional secreted proteins, which can function as acute phase reactants, anti-apoptotic or growth agents (Cancer Biol Ther 2007;6:123)
● REG family members have tropic effect on islets and gastric epithelial cells
● REG IV leads to increased resistance to apoptotic cell death in colorectal carcinoma (Cancer Biol Ther 2006;5:1714)


● Four members identified to date in humans: I alpha, I beta, III and IV
● Also called RELP


● Potent activator of EGFR receptor/Akt/AP-1 signaling pathway in colon cancer cells
● Closely linked with inhibition of apoptosis
● Uprelated in gastric intestinal metaplasia and adenoma (Hum Pathol 2010;41:59)

Uses by pathologists

● No significant uses at this time

Micro images

Colon ISH: normal colon, ulcerative colitis, dysplasia, carcinoma

Gastric cancer

Prostate: normal and carcinoma

Positive staining - normal

● Constitutively expressed in neuroendocrine cells of intestinal mucosa

Positive staining - disease

● Colorectal and gastric signet ring carcinoma (Am J Surg Pathol 2008;32:1182); also metaplastic cells that often accompany gastric carcinoma
● Gallbladder carcinoma; may be related to intestinal metaplasia; serum levels decrease after surgery (Hum Pathol 2009;40:1686)
● Prostatic adenocarcinoma (Clin Cancer Res 2005;11:2237)
● Urachal adenocarcinoma (Am J Surg Pathol 2011;35:787)
● Neuroendocrine neoplasms, but NOT pancreatic islet tumor, paraganglioma, pheochromocytoma (Histol Histopathol 2010;25:63)

Negative staining

● Pancreatic islet tumor, paraganglioma, pheochromocytoma
● Breast and lung signet ring carcinoma (Am J Surg Pathol 2008;32:1182)

End of Stains > Reg IV

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